Small-animal Scanner Research Articles

Image quality phantom and parameters for high spatial resolution small-animal SPECT

At present, generally accepted standards to characterize small-animal single photon emission tomographs (SPECT) do not exist. Whereas for small-animal positron emission tomography (PET), the NEMA NU 4-2008 guidelines are available, such standards are still lacking for small-animal SPECT. More specifically, a dedicated image quality (IQ) phantom and corresponding IQ parameters are absent. The structures of the existing PET IQ phantom are too large to fully characterize the sub-millimeter spatial resolution of modern multi-pinhole SPECT scanners, and its diameter will not fit into all scanners when operating in high spatial resolution mode. We therefore designed and constructed an adapted IQ phantom with smaller internal structures and external diameter, and a facility to guarantee complete filling of the smallest rods. The associated IQ parameters were adapted from NEMA NU 4. An additional parameter, effective whole-body sensitivity, was defined since this was considered relevant in view of the variable size of the field of view and the use of multiple bed positions as encountered in modern small-animal SPECT scanners. The usefulness of the phantom was demonstrated for 99m Tc in a USPECT-II

A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier.

Approximately one-third of epilepsy patients are pharmacoresistant. Overexpression of P-glycoprotein and other multidrug transporters at the blood-brain barrier is thought to play an important role in drug-refractory epilepsy. Thus, quantification of regionally different P-glycoprotein activity in the brain in vivo is essential to identify P-glycoprotein overactivity as the relevant mechanism for drug resistance in an individual patient. Using the radiolabeled P-glycoprotein substrate (R)-[(11)C]verapamil and different doses of coadministered tariquidar, which is an inhibitor of P-glycoprotein, we evaluated whether small-animal positron emission tomography can quantify regional changes in transporter function in the rat brain at baseline and 48 h after a pilocarpine-induced status epilepticus. P-glycoprotein expression was additionally quantified by immunohistochemistry. To reveal putative seizure-induced changes in blood-brain barrier integrity, we performed gadolinium-enhanced magnetic resonance scans on a 7.0 tesla small-animal scanner. Before P-glycoprotein modulation, brain uptake of (R)-[(11)C]verapamil was low in all regions investigated in control and post-status epilepticus rats. After administration of 3 mg/kg tariquidar, which inhibits P-glycoprotein only partially, we observed increased regional differentiation in brain activity uptake in post-status epilepticus versus control rats, which diminished after maximal P-glycoprotein inhibition. Regional increases in the efflux rate constant k(2), but not in distribution volume V(T) or influx rate constant K(1), correlated significantly with increases in P-glycoprotein expression measured by immunohistochemistry. This imaging protocol proves to be suitable to detect seizure-induced regional changes in P-glycoprotein activity and is readily applicable to humans, with the aim to detect relevant mechanisms of pharmacoresistance in epilepsy in vivo.

Refining the sensory and motor ratunculus of the rodent upper extremity: evaluation of the C7 nerve root using fMRI and direct nerve stimulation.

Since the 1980s, the C7 nerve root has gained clinical relevance as a donor nerve in severe brachial plexus root avulsion injuries. Despite success with the cross-chest C7 nerve transfer, inducing injury on an otherwise normal side hinders global acceptance. By sacrificing the C7 nerve root, a predictable pattern of transient sequelae is seen, including extensor weakness and index and middle finger anesthesia. The purpose of this study is to observe cortical activity during direct stimulation of the C7 nerve root using blood oxygen level dependent functional magnetic resonance imaging (fMRI) in a rat model. A total of 12 male Sprague-Dawley rats, weighing 200-250g, were used in this study. Following an acclimation period of 1week, 12 rats underwent exposure and dissection of the brachial plexus. Seven rats underwent placement of an implantable electrode (AISI 304, Plastics1, Roanoke, VA, USA) on the C7 nerve root, while five rats underwent electrode placement on the radial nerve. All animals then underwent fMRI during direct nerve stimulation. Ten consecutive coronal images were obtained during nerve stimulation, using a 9.4-T small-animal MRI scanner. Cortical activation is seen within a very specific area of the primary sensory region of the forelimb during C7 nerve root stimulation. The cortical activation seen during radial nerve stimulation includes that seen during C7 stimulation but extends several slices caudally. The sensory representation of the C7 nerve root is seen in only a small area in the S1FL region compared to that seen in the terminal branches of the brachial plexus. However, this area shows a significant overlap with the S1FL area of activation seen during radial nerve stimulation. This makes sense as the C7 nerve root contributes some, but not all, sensory axons to the radial nerve. Mapping of the C7 cortical representation in the rat brain not only adds to the ongoing development of the motor and sensory ratunculus but also provides an important foundation to study subsequent C7 donor nerve models.

Application of Silicon Photomultipliers to Positron Emission Tomography

Historically, positron emission tomography (PET) systems have been based on scintillation crystals coupled to photomultipliers tubes (PMTs). However, the limited quantum efficiency, bulkiness, and relatively high cost per unit surface area of PMTs, along with the growth of new applications for PET, offers opportunities for other photodetectors. Among these, small-animal scanners, hybrid PET/MRI systems, and incorporation of time-of-flight information are of particular interest and require low-cost, compact, fast, and magnetic field compatible photodetectors. With high quantum efficiency and compact structure, avalanche photodiodes (APDs) overcome several of the drawbacks of PMTs, but this is offset by degraded signal-to-noise and timing properties. Silicon photomultipliers (SiPMs) offer an alternative solution, combining many of the advantages of PMTs and APDs. They have high gain, excellent timing properties and are insensitive to magnetic fields. At the present time, SiPM technology is rapidly developing and therefore an investigation into optimal design and operating conditions is underway together with detailed characterization of SiPM-based PET detectors. Published data are extremely promising and show good energy and timing resolution, as well as the ability to decode small scintillator arrays. SiPMs clearly have the potential to be the photodetector of choice for some, or even perhaps most, PET systems.

Effect of Object Size on Scatter Fraction Estimation Methods for PET—A Computer Simulation Study

Scatter fraction ( <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SF</i> ) for PET scanners is typically estimated by making a single measurement using a solid cylindrical phantom with a line source radially offset from the center. The radial displacement of the line source is expected to give a value for scatter fraction that is representative of a typical PET scan for a scanner. A range of phantom sizes suitable for small animal and whole-body PET scanners is investigated. For whole-body imaging, we simulate phantom diameters ranging from 15 to 42 cm, whereas for small animal scanners, we simulate phantom diameters ranging from 2.5 to 15 cm. We find that the line source displacements suggested by the NEMA NU 4-2008 for three phantoms results in a scatter fraction very similar to the one that would arise from uniformly activated phantoms of similar size. On the other hand, the 20 cm phantom used for count rate performance assessment for wholebody scanners is shown to overestimate by about 25% the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SF</i> of the corresponding uniform phantom, a result that agrees well with that reported by the NEMA committee for the NU 2-2001 standard protocol. Combining the results obtained with small animal and whole-body scanners, we show that the optimal displacement of the line source for estimating the scatter fraction of an equivalent uniformly filled phantom is well approximated by a linear function of the phantom radius and is only weakly dependent on scanner size or detector material. The optimum radial displacement position appears to be at approximately four-fifths of the phantom radius from the center.

Assessment of IP injection of [ 18F]fallypride for behavioral neuroimaging in rats

Great progress has been made toward using small animal PET to assess neurochemical changes during behavior. [ 18F]fallypride (FAL) is a D 2/D 3 antagonist that is sensitive to changes in endogenous dopamine, and, in theory, could be used to assess changes in dopamine during behavioral paradigms. Tail vein injections of tracer require restraint in awake animals, and catheter implantation is invasive and can cause logistical problems. Thus, administering tracer with IP injections (which are well-tolerated by rodents) would be preferable. The purpose of this study was to determine whether IP injection of FAL would produce striatal uptake similar to that seen with traditional IV tail vein injection protocols. Four male Sprague–Dawley rats underwent IP injection of FAL, followed by a 30-min uptake and subsequent dynamic image acquisition on the IndyPET III small animal scanner. Three of these rats also received traditional dynamic scanning with IV FAL injection via a tail vein. Two rats that received IP injection had moderate striatal uptake, with striatum/cerebellum ratios (SUVR) that were only ∼20% lower than ratios from IV scans. Two other rats had little to no uptake; SUVR values were ∼70% lower than IV SUVR. These latter two animals showed heavy bone uptake, evidence of defluorination of FAL. The results of this pilot study suggest that it may be possible to achieve striatal uptake of FAL after IP injection. However, this was not seen consistently across animals. Future studies are needed to validate, and then to optimize, the use of IP FAL for behavioral imaging protocols.

GATE Simulations of Human and Small Animal PET for Determination of Scatter Fraction as a Function of Object Size

In 2D-mode positron emission tomography (PET), scatter is either compensated by approximate methods based on the existing emission data or ignored altogether as the magnitude of the scatter fraction (SF) is on the order of 10%-20%. In clinical PET studies, however, attenuation and sophisticated scatter correction methods are required along with CT or radionuclide transmission scans. With the growing interest in small animal imaging, these correction methods are being translated to small animal scanners, but there is little scientific information about the requirements associated with smaller size objects and scatter geometries. In this study, we focused on the magnitude of the scatter through a series of scatter fraction simulations. To determine the scatter as a function of object size, we performed Monte Carlo simulations using GATE (Geant4 application for emission tomography). Models of the ECAT HR+ PET scanner (included in the GATE package) and the Siemens Inveon small animal scanner (generated by the first author) were used. Simulations were performed for several digital phantoms including the NEMA, XCAT and MOBY phantoms over a wide range of sizes. Small animal NEMA-like phantoms indicated that for cylindrical objects less than 5 cm diameters (encompassing small rats and all mice), the scatter fraction was lower than 17.5% for the 350-650 keV and 20% for the 250-750 keV windows. Similar values were obtained for the MOBY phantoms for the respective sizes. On the other hand, the scatter fraction was more than 35% for even the smallest size human NEMA-like and XCAT phantoms. These results suggest that sophisticated scatter correction methods may not be required for the indicated sizes of mice and rats.

A fillable micro-hollow sphere lesion detection phantom using superposition

The lesion detection performance of SPECT and PET scanners is most commonly evaluated with a phantom containing hollow spheres in a background chamber at a specified radionuclide contrast ratio. However, there are limitations associated with a miniature version of a hollow sphere phantom for small-animal SPECT and PET scanners. One issue is that the ‘wall effect’ associated with zero activity in the sphere wall and fill port causes significant errors for small diameter spheres. Another issue is that there are practical difficulties in fabricating and in filling very small spheres (<3 mm diameter). The need for lesion detection performance assessment of small-animal scanners has motivated our development of a micro-hollow sphere phantom that utilizes the principle of superposition. The phantom is fabricated by stereolithography and has interchangeable sectors containing hollow spheres with volumes ranging from 1 to 14 µL (diameters ranging from 1.25 to 3.0 mm). A simple 60° internal rotation switches the positions of three such sectors with their corresponding background regions. Raw data from scans of each rotated configuration are combined and reconstructed to yield superposition images. Since the sphere counts and background counts are acquired separately, the wall effect is eliminated. The raw data are subsampled randomly prior to summation and reconstruction to specify the desired sphere-to-background contrast ratio of the superposition image. A set of images with multiple contrast ratios is generated for visual assessment of lesion detection thresholds. To demonstrate the utility of the phantom, data were acquired with a multi-pinhole SPECT/CT scanner. Micro-liter syringes were successful in filling the small hollow spheres, and the accuracy of the dispensed volume was validated through repeated filling and weighing of the spheres. The phantom's internal rotation and the data analysis process were successful in producing the expected superposition images. Visual inspection of the multi-contrast images provided simple determination of lesion detection thresholds for this scanner (4:1 ratio for 1.5 mm spheres and 3:1 ratio for 2.0 mm spheres) at a specified cumulated background concentration (30 kBq-min µL−1). In summary, the micro-hollow sphere phantom demonstrated its practical utility for lesion detection evaluation and is well suited for comparing the task-based performance of small-animal SPECT and PET scanners.

Performance evaluation of SiPM photodetectors for PET imaging in the presence of magnetic fields

The multi-pixel photon counter (MPPC) or silicon photomultiplier (SiPM), recently introduced as a solid-state photodetector, consists of an array of Geiger-mode photodiodes (microcells). It is a promising device for PET due to its potential for high photon detection efficiency (PDE) and its foreseeable immunity to magnetic fields. It is also easy to use with simple read-outs, has a high gain and a small size. In this work we evaluate the in field performance of three 1×1 mm 2 (with 100, 400 and 1600 microcells, respectively) and one 6×6 mm 2 (arranged as a 2×2 array) Hamamatsu MPPCs for their use in PET imaging. We examine the dependence of the energy resolution and the gain of these devices on the temperature and reverse bias voltage, when coupled to LYSO scintillator crystals under conditions that one would find in a PET system. We find that the 400 and 1600 microcells models and the 2×2 array are suitable for small-size crystals, like those employed in high resolution small animal scanners. We have confirmed the good performance of these devices up to magnetic fields of 7 T as well as their suitability for performing PET acquisitions in the presence of fast switching gradients and high duty radiofrequency MRI sequences.

Magnetic resonance imaging of hypoxic injury to the murine placenta

We assessed the use of magnetic resonance imaging (MRI) to define placental hypoxic injury associated with fetal growth restriction. On embryonic day 18.5 (E18.5) we utilized dynamic contrast-enhanced (DCE)-MRI on a 4.7-tesla small animal scanner to examine the uptake and distribution of gadolinium-based contrast agent. Quantitative DCE parameter analysis was performed for the placenta and fetal kidneys of three groups of pregnant C57BL/6 mice: 1) mice that were exposed to Fi(O(2)) = 12% between E15.5 and E18.5, 2) mice in normoxia with food restriction similar to the intake of hypoxic mice between E15.5 and E18.5, and 3) mice in normoxia that were fed ad libitum. After imaging, we assessed fetoplacental weight, placental histology, and gene expression. We found that dams exposed to hypoxia exhibited fetal growth restriction (weight reduction by 28% and 14%, respectively, P < 0.05) with an increased placental-to-fetal ratio. By using MRI-based assessment of placental contrast agent kinetics, referenced to maternal paraspinous muscle, we found decreased placental clearance of contrast media in hypoxic mice, compared with either control group (61%, P < 0.05). This was accompanied by diminished contrast accumulation in the hypoxic fetal kidneys (23%, P < 0.05), reflecting reduced transplacental gadolinium transport. These changes were associated with increased expression of placental Phlda2 and Gcm1 transcripts. Exposure to hypoxia near the end of mouse pregnancy reduces placental perfusion and clearance of contrast. MRI-based DCE imaging provides a novel tool for dynamic, in vivo assessment of placental function.

Reconstructed Image Resolution of the LabPET Small Animal Scanner Measured Using Simulated Partial Volume Effects

PET image resolution is a function of scanner intrinsic resolution and reconstruction method. The purpose of this study was to measure the reconstructed image resolution of the LabPETtrade small animal scanner. A Micro Deluxetrade hot rods phantom was filled with an <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> F solution and scanned. The 3D emission data were rebinned using single slice rebinning with various ring differences. Image reconstruction was performed using FBP and variable MLEM iterations in normal and high resolution modes. To estimate the image resolution, the relative peak recovery values were recorded for each hot rod and compared to simulated values of partial volume recovery coefficients obtained by convolving a 2D-Gaussian model with circles of the known rod diameters. FWHM image resolution was shown to improve from 2.3 to 1.1 mm with 20 to 500 MLEM iterations while FBP had a resolution between 1.7-1.8 mm. Initial measurement of the LabPETtrade transverse image resolution is consistent with that expected from a system with individual detector readout. This methodology is applicable to other PET systems and may be particularly useful when using iterative reconstruction.

Gating in small-animal cardio-thoracic CT

Gating is necessary in cardio-thoracic small-animal imaging because of the physiological motions that are present during scanning. In small-animal computed tomography (CT), gating is mainly performed on a projection base because full scans take much longer than the motion cycle. This paper presents and discusses various gating concepts of small-animal CT, and provides examples of concrete implementation. Since a wide variety of small-animal CT scanner systems exist, scanner systems are discussed with respect to the most suitable gating methods. Furthermore, an overview is given of cardio-thoracic imaging and gating applications. The necessary contrast media are discussed as well as gating limitations. Gating in small-animal imaging requires the acquisition of a gating signal during scanning. This can be done extrinsically (additional hardware, e.g. electrocardiogram) or intrinsically from the projection data itself. The gating signal is used retrospectively during CT reconstruction, or prospectively to trigger parts of the scan. Gating can be performed with respect to the phase or the amplitude of the gating signal, providing different advantages and challenges. Gating methods should be optimized with respect to the diagnostic question, scanner system, animal model, type of narcosis and actual setup. The software-based intrinsic gating approaches increasingly employed give the researcher independence from difficult and expensive hardware changes.

Visualization and Quantification of Intraperitoneal Tumors by In Vivo Computed Tomography Using Negative Contrast Enhancement Strategy in a Mouse Model of Ovarian Cancer

Small animal computed tomography (CT) has poor intrinsic soft tissue contrast, limiting evaluation of intra-abdominal structures. Using standard intravascular-extracellular intravenous contrast (IE-IV) alone is theoretically limited by long acquisition times of traditional small animal scanners that may result in equilibration. We assessed whether a negative contrast strategy of enhancing normal tissue surrounding tumor, instead of the tumor itself, can visualize and quantify intraperitoneal (IP) cancer in a mouse model. Two and a half weeks after IP injection of Hey A8 cells, four groups of three animals each were administered serial dilutions of IV Fenestra LC (RES-IV), oral Gastroview, and IP Optiray 320. Another group of three animals was administered IV Optiray 320 (IE-IV), oral Gastroview, and IP Optiray 320 in successive combinations. Both groups were imaged by CT. Tumor and organ Hounsfield units were measured, and visualization was assessed. With increasing contrast amount, the Hounsfield unit of organs generally increased, whereas that of tumor remained essentially stable. The visualization of abdominal organs and tumor also generally increased with increasing contrast amount. Visualization of tumor and its margins adjacent to liver, spleen, and stomach was significantly better on administering RES-IV. However, for tumor adjacent to bladder, both IE-IV and RES-IV were equivalent. In vivo CT-derived tumor weights correlated highly with ex vivo tumor weights (r = 0.96, P < .0001, n = 15). Thus, CT using negative contrast enhancement strategy allows visualization and quantification of IP tumors. Such a strategy will also enable anatomic localization of functional signal for combination/molecular imaging.

WE-D-303A-03: Magnetic Resonance Temperature Imaging Guided Laser-Induced Thermal Therapy with Multi-Walled Carbon Nanotubes

Purpose: Feasibility has been studied for combining Multi‐Walled Carbon Nanotubes(MWNTs), as a near‐infrared (NIR) laser absorber and heat generator, with ProtonResonance Frequency (PRF) based Magnetic Resonance Temperature Imaging (MRTI), to improve the safety and efficacy of laser‐induced thermal therapy. Method and Materials: MWNTs‐laser‐induced therapy was evaluated using 3 tissue equivalent gel phantoms: alginate‐only (sodium alginate 3g/L), MWNTs‐instilled (0.5mg/ml) and MWNTs‐implanted (sub‐surface, simulating a subcutaneous tumor containing MWNTs).In vivo experiments used 4 RENCA kidneytumor bearing mice in their right flank, thermally treated using an external laser beam after direct MWNTs injection (100ug), and monitored by MRTI throughout the treatment. MRTI‐guided laser‐induced thermal therapy for phantom and in vivo experiments was performed using MR‐compatible laser systems (fiber‐optic and external laser beam) and a 7T MRI small animal scanner (Bruker Biospin). The 3‐D MRTI in vivo protocol has a standard deviation of < 1°C, temporal resolution of 4.2s and a high spatial resolution of 0.25mm. Results: With minimum‐invasive fiber‐optic laser heating (o 0.6mm, 1 min @ 0.1W), phantom results show that the MWNTs—instilled phantom heated preferentially (from 20°C to 47°C; Δt=+27°C), compared to the alginated‐only phantom (from 20°C to 25°C; Δt=+5°C). With non‐invasive laser heating (o 10mm, 0.5 min @ 1.8W), the implanted region of the MWNTs‐implanted phantom showed significantly elevated temperatures compared to the nearby alginate‐only medium (Δt=+15°C). Implanted RENCA kidney flank tumors in mice injected with MWNTs were heated to 77°C (Δt=+51°C) after a single 30s 3W non‐invasive laser irradiation compared to 44°C in the laser‐only tumors (no MWNTs Δt=+18°C). In two weeks post‐treatment study, all control tumors (no MWNT no laser) and laser‐only tumors keep growing while MWNTs‐tumors begin to shrink. Conclusion: This study indicates the significant improvement in small animal laser‐induced thermal therapy and may be applicable for superficial tumors in humans.

Assessment of Airway Distribution of Transnasal Solutions in Mice by PET/CT Imaging

Transnasal administration is one of the most common routes for allergen challenge in mouse models of airway diseases. Although this technique is widely used, neither the amount of allergen that reaches the lung nor its airway distribution has been well established. We used positron emission tomography (PET) and computed tomography (CT) to examine the anatomical distribution of a solution containing a tracer immediately after transnasal delivery and to determine the possible influence of age and administered volume. Forty-six female BALB/c mice were divided into three groups according to instillation volume and age: (A) 15 microl, 8-10 weeks old (N = 10), (B) 30 microl, 8-10 weeks old (N = 20), and (C) 30 microl, 32 weeks old (N = 16). Anesthetized animals underwent a dynamic scan in a dedicated small-animal PET scanner immediately after transnasal administration of a solution containing (18)FDG. Regions of interest were used to obtain quantitative data. Animals were also imaged with a small-animal CT scanner to obtain complementary anatomical information. Mean +/- SD (5.69 +/- 4.51%) of the solution administered reached the lungs in group A, 41.84 +/- 8.03% in group B, and 36.65 +/- 16.15% in group C. A comparable percentage was delivered to the left and right lungs in all the groups. Analysis of variance revealed a significant difference between the groups in the proportion of the solution that reached the lungs depending on the injection volume (P < 0.001), but not depending on animal age. In this first report on quantitative imaging by PET and CT in small animals, we confirmed the suitability of the transnasal route with an instilled volume of 30 microl delivering fluids into the lower airways, although only about 40% of the dose reaches the lungs.

In-vivo imaging characteristics of two fluorinated flumazenil radiotracers in the rat

[(11)C]Flumazenil shows promise as a clinical and research PET radiotracer to image changes in GABA(A) central benzodiazepine receptor (cBZR), but its widespread use has been limited by practical limitations of [(11)C]. This study evaluated the imaging characteristics of two fluorinated PET radiotracers in rats in vivo: [(18)F]fluoroflumazenil ([(18)F]FFMZ) and [(18)F]flumazenil ([(18)F]FMZ). PET acquisitions were performed on a small-animal scanner following injection of [(18)F]FFMZ in nine rats and [(18)F]FMZ in eight rats. The following treatments were investigated: (1) injection of the tracer dose, (2) presaturation then injection of the tracer dose, and (3) injection of the tracer dose followed by a displacement injection. Unchanged tracer was measured in plasma and brain structures in four animals 10 and 30 min after injection, and ex-vivo autoradiography was also performed. For both [(18)F]FFMZ and [(18)F]FMZ maximal brain activity peaked rapidly, and was highest in the hippocampus (1.12+/-0.06 SUV, 1.24+/-0.10 SUV, respectively), and lowest in the pons (1.00+/-0.07 SUV, 1.03+/-0.09 SUV, respectively). By 50 min after injection, maximal uptake for [(18)F]FFMZ and [(18)F]FMZ had decreased in the hippocampus to 18+/-3% and 80+/-1% (p<0.01), respectively. The presaturation and displacement studies showed a higher nonspecific component for [(18)F]FFMZ than for [(18)F]FMZ. Metabolite studies showed that at 30 min only 10% of the signal was from [(18)F]FFMZ in the brain. This nonspecific binding was apparent on autoradiography. In contrast, [(18)F]FMZ accounted for >70% of the signal in the brain, which resulted in well-defined regional binding on autoradiography. These results demonstrate that [(18)F]FMZ is a superior radiotracer to [(18)F]FFMZ for in-vivo PET imaging of the GABA(A)/cBZR, having slower metabolism and leading to lower concentrations of metabolites in the brain that results in a substantially better signal-to-noise ratio.

The Hardware and Signal Processing Architecture of LabPET™, a Small Animal APD-Based Digital PET Scanner

The highly multiplexed analog processing front-end of current Positron Emission Tomography (PET) scanners yields high accuracy for timing but adds significant dead time and offers little flexibility for improvement. A new fully digital APD-based scanner architecture is proposed wherein nuclear pulses are sampled directly at the output of the Charge Sensitive Preamplifier (CSP) with one free-running ADC per channel. This approach offers the opportunity to explore new digital signal processing algorithms borrowed from other fields like command and control theory, as well as advanced heuristics such as neural networks. The analog front-end consists of a dedicated 0.18- mum, 16-channel CMOS charge sensitive preamplifier. Digitization is performed with off-the-shelf dual 8-bit analog-to-digital converters running at 45-MSPS. Digital processing is shared between a FPGA and a Digital Signal Processor (DSP), which can process the data from up to 64 parallel channels without dead time. The FPGA deals with the initial signal analysis for energy measurement and time stamping, while crystal identification is deferred to the DSP running computation-intensive recursive algorithms. The entire system is controlled serially through a Firewire link by a Graphic User Interface. The initial LabPETtrade implementation of the system is a dedicated small animal scanner holding up to 4608 APD channels at an averaged count rate of up to 10 000 events/s each.

Imaging tumour-bearing animals using clinical scanners

Purpose: We investigated the capability of small animal imaging in clinical scanners for cancer research focusing on positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI).Methods and materials: We summarise basic principles, benefits and drawbacks of imaging modalities and discuss issues associated with animal welfare during imaging and its related effects on imaging results based on data from literature supplemented by own experiences.Results: MRI of tumour-bearing mice and rats in the clinical scanner is well-established for morphological and functional imaging in oncology. Clinical PET/CT did not yet establish as a research tool due to limited resolution and sensitivity, but its feasibility for tumour imaging has been demonstrated in mice. Anesthesia, animal handling and application of substances (e.g., contrast media) may alter animal physiology and, thus, also influence imaging results.Conclusions: Small animal imaging in clinical scanners offers good image quality and presents an alternative to dedicated small animal scanners for numerous applications in cancer research. Successful and meaningful small animal imaging in clinical as well as dedicated scanners prerequisites a thorough knowledge of animal morphology and physiology, a deep understanding of likely influences of animal manipulation on imaging and an adequate care for animal welfare.

Dopamine transporter binding in rat striatum: a comparison of [O-methyl-11C]β-CFT and [N-methyl-11C]β-CFT

Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [(11)C]beta-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [(11)C]beta-CFT is commonly labeled at the N-methyl position. However, labeling of [(11)C]beta-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [(11)C]beta-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-(11)C]beta-CFT and once with [O-methyl-(11)C]beta-CFT. DAT binding potentials (BP identical withB'(avail)/K(d)) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. [N-Methyl-(11)C]beta-CFT and [O-methyl-(11)C]beta-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258+/-30 GBq/micromol. Average BP values for right and left striata with [N-methyl-(11)C]beta-CFT were 1.16+/-0.08 and 1.23+/-0.14, respectively. BP values for [O-methyl-(11)C]beta-CFT were 1.18+/-0.08 (right) and 1.22+/-0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. These results suggest that [O-methyl-(11)C]beta-CFT is quantitatively equivalent to [N-methyl-(11)C]beta-CFT in the rat striatum.

Molecular Imaging of the Pancreas in Small Animal Models

Recent advances in several imaging modalities have improved noninvasive assessment of the pancreas in preclinical animal models and have enabled sequential studies in the same animal, permitting dynamic studies of pancreatic disease. This review outlines progress in the application of small animal imaging to monitor the pancreatic islet, insulitis, and pancreatitis. Preclinical advances in magnetic resonance imaging (MRI) and positron emission tomography (PET) have benefited from higher magnetic field strengths and dedicated small animal scanners, respectively.